PXD019430 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | VAV3 in ERBB4-mediated cancer cell migration |
Description | ERBB4 is a member of the epidermal growth factor receptor (EGFR)/ERBB subfamily of receptor tyrosine kinases that regulates cellular processes including proliferation, migration and survival. ERBB4 signaling is involved in embryogenesis and homeostasis of adult tissues, but also in human pathologies such as cancer, neurological disorders and cardiovascular diseases. A mass spectrometry screen revealed guanine nucleotide exchange factor (GEF) VAV3, an activator of Rho family GTPases, as a novel ERBB4-interacting protein in breast cancer cells. The ERBB4-VAV3-interaction was confirmed by targeted mass-spectrometry, coimmunoprecipitation experiments, and further defined by demonstrating that kinase activity and tyrosine residues 1022 and 1162 of ERBB4, as well as the intact phosphotyrosine-interacting SH2 domain of VAV3 were necessary for the interaction. ERBB4 was also shown to stimulate tyrosine phosphorylation of the VAV3 activation domain, which is required for GEF activity of VAV proteins. In addition to VAV3, also the other members of the VAV family, VAV1 and VAV2 were shown to coprecipitate with ERBB4. Analyses of the effects of overexpression of dominant-negative VAV3 constructs or downregulation of VAV3 expression by shRNAs in breast cancer cells demonstrated that active VAV3 was involved in ERBB4-stimulated migration. These findings define the VAV GTPases as novel effectors of ERBB4 activity in a signaling pathway relevant for cancer cell migration. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:07:41.873.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Johannes Merilahti |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-05-27 17:21:29 | ID requested | |
1 | 2020-06-23 22:15:02 | announced | |
⏵ 2 | 2024-10-22 05:07:42 | announced | 2024-10-22: Updated project metadata. |
Publication List
10.1074/jbc.ra119.010925; |
Ojala VK, Knittle AM, Kirjalainen P, Merilahti JAM, Kortesoja M, Tvorogov D, Vaparanta K, Lin S, Kast J, Pulliainen AT, Kurppa KJ, Elenius K, The guanine nucleotide exchange factor VAV3 participates in ERBB4-mediated cancer cell migration. J Biol Chem, 295(33):11559-11571(2020) [pubmed] |
Keyword List
submitter keyword: VAV3, Targeted analysis, PRM,ERBB4 |
Contact List
Klaus Elenius |
contact affiliation | Institute of Biomedicine, and Medicity Research Laboratories, University of Turku, Turku, Finland; Turku Bioscience Centre, University of Turku, and Åbo Akademi University, Turku, Finland |
contact email | klaus.elenius@utu.fi |
lab head | |
Johannes Merilahti |
contact affiliation | Turku Bioscience University of Turku |
contact email | johannes.merilahti@utu.fi |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD019430
- Label: PRIDE project
- Name: VAV3 in ERBB4-mediated cancer cell migration